How we use pazopanib in treating soft-tissue sarcoma: experience at our multidisciplinary sarcoma centers

Abstract

Objective: Soft-tissue sarcomas (STSs) are rare malignant tumors arising from tissues of mesenchymal origin throughout the body with poor prognosis in advanced disease. This commentary describes the current treatment landscape for patients with advanced STS undergoing chemotherapy as well as how pazopanib, a newer multitargeted tyrosine kinase inhibitor, has been incorporated into treatment for different subtypes of STS in our clinical practice.

Methods: PubMed was searched (2010–2015) for articles involving the treatment and management of advanced STS. Key search terms included “soft tissue sarcoma”, “pazopanib”, “chemotherapy”, “doxorubicin”, “ifosfamide”, “trabectedin” and “gemcitabine”. Additionally, ClinicalTrials.gov was searched to identify ongoing studies evaluating pazopanib in STS. Reference citations within relevant articles revealed further sources of value.

Results: Standard treatment for advanced STS is single agent or combination systemic chemotherapy. The efficacy of these treatments varies widely, likely because of tumor heterogeneity and cellular mechanisms of chemoresistance, and adverse effects may be a limiting factor for combination therapy. Pazopanib, approved for the treatment of advanced STS in patients who received prior chemotherapy, has demonstrated clinical benefit in a variety of histologic types of advanced STS where the prognosis is often poor. While pazopanib has a favorable safety profile compared with commonly prescribed chemotherapies, it has several safety concerns and dose-limiting adverse effects. We share our best practice for managing adverse events to ensure patient tolerability.

Conclusions: Use of pazopanib increases the treatment options available to control advanced STS, with management of adverse events through close monitoring, patient education and treatment as necessary.

Keywords:

• Pazopanib
• sarcoma
• soft tissue
• neoplasms
• angiogenesis inhibitors
• molecular targeted therapy
• individualized medicine

Transparency

Declaration of funding

Editorial support was funded by Novartis Pharmaceuticals Inc.

Author contributions: B.A.V.T. and J.C.T were involved in the conception, design, analysis and interpretation of the data; revising the paper critically for intellectual content; and final approval of the version to be published. Both authors agree to be accountable for all aspects of the work.

Declaration of financial/other relationships

B.A.V.T. has disclosed that he has received consulting fees from GlaxoSmithKline, Novartis, Lilly, EMD Serono, Aventis, Janssen, Caris and Karyopharm; and research funding from Polaris and Morphotek. J.C.T. has disclosed that he has received consulting fees from Bayer, EMD Serono, Janssen and Novartis; and research funding from Janssen, Morphotek, Plexxikon and Agios.

CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

The authors thank Harleigh E. Willmott PhD CMPP from ApotheCom, Yardley, Pennsylvania, USA for editorial assistance, which was funded by Novartis Pharmaceuticals Inc.